ROBUSTAFLAVONE, A POTENTIAL NONNUCLEOSIDE ANTI-HEPATITIS-B AGENT

Robustaflavone, a naturally occurring biflavanoid isolated from Rhus s uccedanea, was found to be a potent inhibitor of hepatitis B virus (HB V) replication in 2.2.15 cells, with an effective concentration (EC50) of 0.25 mu M, and a selectivity index (SI, IC50/EC90) of 153. Robusta flavone hexaacetate inhibited HBV replication with an EC50 of 0.73 mu M, but exhibited no cytotoxicity at concentrations up to 1000 mu M. Co mbinations of robustaflavone with penciclovir and lamivudine displayed synergistic anti-HBV activity, having the most pronounced effects whe n the combination ratios were similar to the ratio of EC50 potencies. Thus, a 1:1 combination of robustaflavone and penciclovir exhibited an EC50 of 0.11 mu M and an SI of 684, while a 10:1 combination of robus taflavone and lamivudine exhibited an EC50 of 0.054 mu M and an SI of 894. Statistical analyses of the combination data using the Combostat (R) program confirmed that robustaflavone exhibited synergism with bot h penciclovir and lamivudine. (C) 1998 Elsevier Science B.V. All right s reserved.